Koshiol Jill, Gao Yu-Tang, Dean Michael, Egner Patricia, Nepal Chirag, Jones Kristine, Wang Bingsheng, Rashid Asif, Luo Wen, Van Dyke Alison L, Ferreccio Catterina, Malasky Michael, Shen Ming-Chang, Zhu Bin, Andersen Jesper B, Hildesheim Allan, Hsing Ann W, Groopman John
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Gastroenterology. 2017 Aug;153(2):488-494.e1. doi: 10.1053/j.gastro.2017.04.005. Epub 2017 Apr 17.
BACKGROUND & AIMS: Aflatoxin, which causes hepatocellular carcinoma, may also cause gallbladder cancer. We investigated whether patients with gallbladder cancer have higher exposure to aflatoxin than patients with gallstones.
We measured aflatoxin B (AFB)-lysine adducts in plasma samples from the Shanghai Biliary Tract Cancer case-control study, conducted from 1997 through 2001. We calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and the population-attributable fraction for 209 patients with gallbladder cancer and gallstones vs 250 patients with gallstones without cancer (controls). In 54 patients with gallbladder cancer, tumor tissue was examined for the R249S mutation in TP53, associated with aflatoxin exposure, through targeted sequencing.
The AFB-lysine adduct was detected in 67 (32%) of 209 patients with gallbladder cancer and 37 (15%) of the 250 controls (χ P < .0001), almost threefold more patients with gallbladder cancer than controls (OR, 2.71; 95% CI, 1.70-4.33). Among participants with detectable levels of AFB-lysine, the median level of AFB-lysine was 5.4 pg/mg in those with gallbladder cancer, compared with 1.2 pg/mg in controls. For patients in the fourth quartile of AFB-lysine level vs the first quartile, the OR for gallbladder cancer was 7.61 (95% CI, 2.01-28.84). None of the 54 gallbladder tumors sequenced were found to have the R249S mutation in TP53. The population-attributable fraction for cancer related to aflatoxin was 20% (95% CI, 15%-25%).
In a case-control study of patients with gallbladder cancer and gallstones vs patients with gallstones without cancer, we associated exposure to aflatoxin (based on plasma level of AFB-lysine) with gallbladder cancer. Gallbladder cancer does not appear associate with the R249S mutation in TP53. If aflatoxin is a cause of gallbladder cancer, it may have accounted for up to 20% of the gallbladder cancers in Shanghai, China, during the study period, and could account for an even higher proportion in high-risk areas. If our findings are verified, reducing aflatoxin exposure might reduce the incidence of gallbladder cancer.
黄曲霉毒素可引发肝细胞癌,也可能导致胆囊癌。我们调查了胆囊癌患者与胆结石患者相比,接触黄曲霉毒素的水平是否更高。
我们检测了1997年至2001年进行的上海胆道癌病例对照研究中血浆样本里的黄曲霉毒素B(AFB)-赖氨酸加合物。我们计算了209例胆囊癌和胆结石患者与250例无癌胆结石患者(对照)的年龄和性别调整比值比(OR)及95%置信区间(CI),以及人群归因分数。对54例胆囊癌患者的肿瘤组织进行靶向测序,检测与黄曲霉毒素暴露相关的TP53基因R249S突变。
209例胆囊癌患者中有67例(32%)检测到AFB-赖氨酸加合物,250例对照中有37例(15%)检测到(χ²P <.0001),胆囊癌患者检测到的人数几乎是对照组的三倍(OR,2.71;95% CI,1.70 - 4.33)。在检测到AFB-赖氨酸的参与者中,胆囊癌患者AFB-赖氨酸的中位数水平为5.4 pg/mg,而对照组为1.2 pg/mg。AFB-赖氨酸水平处于第四四分位数的患者与第一四分位数的患者相比,胆囊癌的OR为7.61(95% CI,2.01 - 28.84)。在测序的54个胆囊肿瘤中,未发现TP53基因有R249S突变。黄曲霉毒素相关癌症的人群归因分数为20%(95% CI,15% - 25%)。
在一项胆囊癌和胆结石患者与无癌胆结石患者的病例对照研究中,我们发现黄曲霉毒素暴露(基于血浆AFB-赖氨酸水平)与胆囊癌有关。胆囊癌似乎与TP53基因的R249S突变无关。如果黄曲霉毒素是胆囊癌的病因,在研究期间,它可能导致了中国上海高达20%的胆囊癌病例,在高危地区所占比例可能更高。如果我们的研究结果得到证实,减少黄曲霉毒素暴露可能会降低胆囊癌的发病率。